Senile dementia, Alzheimer's type (SDAT) is one of the most common, yet most poorly understood of neurologic disorders. The principle neuropathologic lesion encountered in the brains of patients with SDAT is theneurofibrillary tangle (NFT). Recent studies have pointed to the possible role of excess aluminum in the pathogenesis of SDAT. Using scanning electron microscopy in conjunction with electron probe analysis, we have developed techniques for the determination of intraneuronal trace element analysis. Using these techniques we have identified intraneuronal accumulations of aluminum within neurofibrillary tangle-bearing cells in the hippocampus and frontal cortex of patients with SDAT. With this as a basis, we have begun to study the intraneuronal trace element composition of brain specimens derived from the Chamorros of Guam. The Chamorros are a people characterized by a striking propensity to extensive NFT formation. This tendency among the Chamorros is also accompanied by an exceedingly high incidence of ALS and Parkinsonism with severe dementia (PD). Preliminary data indicate that tangle-bearing hippocampal neurons in these cases also demonstrate significant aluminum accumulations. Epidemiologic evidence suggests that these intracellular accumulations are associated with local environmental factors on Guam related to water and soil conditions. We intend to collect a series of brain tissue samples of Guananian ALS and PD cases and non-impaired controls, as well as a comparable series of ALS, idiopathic Parkinsonism and SDAT cases and normal controls from the mainland U.S. Intracellular trace element analysis will be performed on neurons within the hippocampus, cortex, and the motor and extraphyramidal systems. Sensitive quantitative measures of tissue levels of several trace elements also will be obtained by atomic absorption spectrometry. These data will provide a means to evaluate the possible role of neurotoxic trace element accumulations in NFT formation, motor neuron and extrapyramidal system degeneration. By analysis of the clinical, metabolic and epidemiologic data avaiable from these cases, we will evaluate potential sources for these element abnormalities.